Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease

GTEx Consortium

doi:10.1016/j.cell.2021.03.050

Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease

GTEx Consortium

Mailman School of Public Health

Résultat de recherche › examen par les pairs

101 Citations (Scopus)

Résumé

Long non-coding RNA (lncRNA) genes have well-established and important impacts on molecular and cellular functions. However, among the thousands of lncRNA genes, it is still a major challenge to identify the subset with disease or trait relevance. To systematically characterize these lncRNA genes, we used Genotype Tissue Expression (GTEx) project v8 genetic and multi-tissue transcriptomic data to profile the expression, genetic regulation, cellular contexts, and trait associations of 14,100 lncRNA genes across 49 tissues for 101 distinct complex genetic traits. Using these approaches, we identified 1,432 lncRNA gene-trait associations, 800 of which were not explained by stronger effects of neighboring protein-coding genes. This included associations between lncRNA quantitative trait loci and inflammatory bowel disease, type 1 and type 2 diabetes, and coronary artery disease, as well as rare variant associations to body mass index.

Langue d'origine	English
Pages (de-à)	2633-2648.e19
Journal	Cell
Volume	184
Numéro de publication	10
DOI	https://doi.org/10.1016/j.cell.2021.03.050
Statut de publication	Published - mai 13 2021

Financement

Bailleurs de fonds	Numéro du bailleur de fonds
LDACC
Marie-Skłodowska Curie fellowship H2020
National Science Foundation	R01HL135313-01
National Institutes of Health
National Institute of Mental Health	R01MH109905, R01MH101822, R01MH107666, R01MH106842
National Institute on Drug Abuse
National Heart, Lung, and Blood Institute	R01HL134817, R01HL139478, R01HL142028, R01HL142015, R33HL120757, R01HL109512
National Human Genome Research Institute	U01HG009080, R01HG008150, R01HG010067, U01HG009431, UM1HG008901
National Cancer Institute
National Institute of Neurological Disorders and Stroke
U.S. National Library of Medicine	HHSN268201000029C, 5U41HG009494, 1K99HG009916-01, R01GM122924, 5T15LM007033-36
School of Medicine, Stanford University	R01MH101814, R01AG066490
Horizon 2020 Framework Programme	706636
Searle Scholars Program	R01GM124486, P30DK020595

ASJC Scopus Subject Areas

General Biochemistry,Genetics and Molecular Biology

ODD de l’ONU

Cette action contribue à la réalisation des objectifs de développement durable suivants

Accès au document

10.1016/j.cell.2021.03.050

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@article{c1e97adb6afc47069cbb9b964bd7d2a2,

title = "Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease",

abstract = "Long non-coding RNA (lncRNA) genes have well-established and important impacts on molecular and cellular functions. However, among the thousands of lncRNA genes, it is still a major challenge to identify the subset with disease or trait relevance. To systematically characterize these lncRNA genes, we used Genotype Tissue Expression (GTEx) project v8 genetic and multi-tissue transcriptomic data to profile the expression, genetic regulation, cellular contexts, and trait associations of 14,100 lncRNA genes across 49 tissues for 101 distinct complex genetic traits. Using these approaches, we identified 1,432 lncRNA gene-trait associations, 800 of which were not explained by stronger effects of neighboring protein-coding genes. This included associations between lncRNA quantitative trait loci and inflammatory bowel disease, type 1 and type 2 diabetes, and coronary artery disease, as well as rare variant associations to body mass index.",

author = "{GTEx Consortium} and {de Goede}, {Olivia M.} and Nachun, {Daniel C.} and Ferraro, {Nicole M.} and Gloudemans, {Michael J.} and Rao, {Abhiram S.} and Craig Smail and Eulalio, {Tiffany Y.} and Fran{\c c}ois Aguet and Bernard Ng and Jishu Xu and Barbeira, {Alvaro N.} and Castel, {Stephane E.} and Sarah Kim-Hellmuth and Park, {Yo Son} and Scott, {Alexandra J.} and Strober, {Benjamin J.} and Shankara Anand and Stacey Gabriel and Getz, {Gad A.} and Aaron Graubert and Kane Hadley and Handsaker, {Robert E.} and Huang, {Katherine H.} and Xiao Li and MacArthur, {Daniel G.} and Meier, {Samuel R.} and Nedzel, {Jared L.} and Nguyen, {Duyen T.} and Segr{\`e}, {Ayellet V.} and Ellen Todres and Brunilda Balliu and Rodrigo Bonazzola and Andrew Brown and Conrad, {Donald F.} and Cotter, {Daniel J.} and Nancy Cox and Sayantan Das and Dermitzakis, {Emmanouil T.} and Jonah Einson and Engelhardt, {Barbara E.} and Eleazar Eskin and Flynn, {Elise D.} and Laure Fresard and Gamazon, {Eric R.} and Diego Garrido-Mart{\'i}n and Gay, {Nicole R.} and Roderic Guig{\'o} and Hamel, {Andrew R.} and Yuan He and Gen Li",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = may,

day = "13",

doi = "10.1016/j.cell.2021.03.050",

language = "English",

volume = "184",

pages = "2633--2648.e19",

journal = "Cell",

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T1 - Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease

AU - GTEx Consortium

AU - de Goede, Olivia M.

AU - Nachun, Daniel C.

AU - Ferraro, Nicole M.

AU - Gloudemans, Michael J.

AU - Rao, Abhiram S.

AU - Smail, Craig

AU - Eulalio, Tiffany Y.

AU - Aguet, François

AU - Ng, Bernard

AU - Xu, Jishu

AU - Barbeira, Alvaro N.

AU - Castel, Stephane E.

AU - Kim-Hellmuth, Sarah

AU - Park, Yo Son

AU - Scott, Alexandra J.

AU - Strober, Benjamin J.

AU - Anand, Shankara

AU - Gabriel, Stacey

AU - Getz, Gad A.

AU - Graubert, Aaron

AU - Hadley, Kane

AU - Handsaker, Robert E.

AU - Huang, Katherine H.

AU - Li, Xiao

AU - MacArthur, Daniel G.

AU - Meier, Samuel R.

AU - Nedzel, Jared L.

AU - Nguyen, Duyen T.

AU - Segrè, Ayellet V.

AU - Todres, Ellen

AU - Balliu, Brunilda

AU - Bonazzola, Rodrigo

AU - Brown, Andrew

AU - Conrad, Donald F.

AU - Cotter, Daniel J.

AU - Cox, Nancy

AU - Das, Sayantan

AU - Dermitzakis, Emmanouil T.

AU - Einson, Jonah

AU - Engelhardt, Barbara E.

AU - Eskin, Eleazar

AU - Flynn, Elise D.

AU - Fresard, Laure

AU - Gamazon, Eric R.

AU - Garrido-Martín, Diego

AU - Gay, Nicole R.

AU - Guigó, Roderic

AU - Hamel, Andrew R.

AU - He, Yuan

AU - Li, Gen

PY - 2021/5/13

Y1 - 2021/5/13

N2 - Long non-coding RNA (lncRNA) genes have well-established and important impacts on molecular and cellular functions. However, among the thousands of lncRNA genes, it is still a major challenge to identify the subset with disease or trait relevance. To systematically characterize these lncRNA genes, we used Genotype Tissue Expression (GTEx) project v8 genetic and multi-tissue transcriptomic data to profile the expression, genetic regulation, cellular contexts, and trait associations of 14,100 lncRNA genes across 49 tissues for 101 distinct complex genetic traits. Using these approaches, we identified 1,432 lncRNA gene-trait associations, 800 of which were not explained by stronger effects of neighboring protein-coding genes. This included associations between lncRNA quantitative trait loci and inflammatory bowel disease, type 1 and type 2 diabetes, and coronary artery disease, as well as rare variant associations to body mass index.

AB - Long non-coding RNA (lncRNA) genes have well-established and important impacts on molecular and cellular functions. However, among the thousands of lncRNA genes, it is still a major challenge to identify the subset with disease or trait relevance. To systematically characterize these lncRNA genes, we used Genotype Tissue Expression (GTEx) project v8 genetic and multi-tissue transcriptomic data to profile the expression, genetic regulation, cellular contexts, and trait associations of 14,100 lncRNA genes across 49 tissues for 101 distinct complex genetic traits. Using these approaches, we identified 1,432 lncRNA gene-trait associations, 800 of which were not explained by stronger effects of neighboring protein-coding genes. This included associations between lncRNA quantitative trait loci and inflammatory bowel disease, type 1 and type 2 diabetes, and coronary artery disease, as well as rare variant associations to body mass index.

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DO - 10.1016/j.cell.2021.03.050

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AN - SCOPUS:85105565888

SN - 0092-8674

VL - 184

SP - 2633-2648.e19

JO - Cell

JF - Cell

IS - 10

ER -

Population-scale tissue transcriptomics maps long non-coding RNAs to complex disease

Résumé

Financement

ASJC Scopus Subject Areas

ODD de l’ONU

Accès au document

Autres fichiers et liens

Empreinte numérique

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